Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

1110 Chapter 20: Cancer
tumor
suppressor
gene
mutation
heritable gene silencing in
condensed chromatin
CANCER
= genetic change
= epigenetic change
Figure 20–22 The pathways leading to
loss of tumor suppressor gene function
in cancer involve both genetic and
epigenetic changes. (A) As indicated, the
changes that silence tumor suppressor
genes can occur in any order. Both DNA
methylation and the packaging of a gene
into condensed chromatin can prevent
its expression in a way that is inherited
when a cell divides (see Figure 4–44).
(B) The frequency of gene silencing by
hypermethylation observed in four different
types of cancer. The five genes listed at the
top can all function as tumor suppressor
genes; BRCA1 and hMLH1 affect genome
stability and are in the subclass known as
genome maintenance genes. ND, no data.
(Adapted from M. Esteller et al., Cancer
Res. 61:3225–3229, 2001.)
(A)
p16 INK4A
p14 ARF
BRCA1
hMLH1
APC
p16 INK4A
p14 ARF
BRCA1
hMLH1
APC
p16 INK4A
p14 ARF
BRCA1
hMLH1
frequency of
hypermethylation
APC
p16 INK4A
p14 ARF
BRCA1
hMLH1
APC
(B)
40
30
20
10
0
BREAST COLON/RECTUM STOMACH LUNG
ND
deletion or duplication, without the need for complete sequence information.
The genome can be scanned for epigenetic changes. And finally, alterations in
levels of gene expression can be systematically determined by analysis of mRNAs
(see Figure 7–3). These approaches generally involve comparing cancer cells with
normal controls—ideally, noncancerous cells originating in the same tissue and
from the same patient.
MBoC6 m20.32/20.22
oncogene
N
(A)
tumor suppressor gene
N
(B)
missense mutation
truncating mutation
kinase domain
domain that binds a
transcription regulator
C
C
Figure 20–23 The distinct types of DNA
sequence changes found in oncogenes
compared to tumor suppressor
genes. In this diagram, mutations that
change an amino acid are denoted by
blue arrowheads, whereas mutations
that truncate the polypeptide chain are
marked by yellow arrowheads. (A) As in
this example, oncogene mutations can
be detected by the fact that the same
nucleotide change is repeatedly found
among the missense mutations in a
gene. (B) For tumor suppressor genes, by
contrast, missense mutations that abort
protein synthesis by creating stop codons
predominate. (Adapted from B. Vogelstein
et al., Science 339:1546–1558, 2013.)